Issue link: https://www.e-digitaleditions.com/i/507774
cially, including GlaxoSmithKline, AstraZeneca, and Jannsen in Europe. In Mexico, generics manufacturer Chinion makes three products with GEA's equipment. The company also has three or four installations in South Korea and six or seven in Japan, including at Diaichi Sankyo. The equipment is also used at Vertex of Boston, MA, and in Pfizer's PCCM approach. Several questions about cleaning arose. Schoeters said running the system empty, what he called a dry rinse, was the first step. Next, the components must be removed and cleaned offline. One customer runs its tabletting line for 2 or 3 weeks before cleaning and reassembling the components, which takes 2 days. He said the job could be done faster if everything were done simultaneously instead of having one person clean the parts one by one. Aditya Vanarase, a research investigator at Bristol- Myers Squibb, spoke about the key role of loss-in-weight feeders and blenders in solid dosage continuous manufac- turing. Advantages of continuous mixing include less risk of particle segregation, less post-blending powder han- dling, and the potential to avoid roller compaction/wet granulation. She presented case studies about optimizing feeder refill and dealing with cohesive materials in con- tinuous mixers. Vanarase also covered the practical aspects of feeder selection, including desired feed rate, feeder scale, capac- ity, nozzle size, gear ratio, powder properties, type of screw, and discharge screens. A case study examined how the feeder responded to variation in material properties. Development challenges of the future include implement- ing advanced process control, rejecting off-spec material, modeling predictive controls, and designing formulations suitable for continuous processes. Eric Jayjock of Janssen Pharmaceutical, Horsham, PA, performed his graduate studies at Rutgers University, where he was a part of the Center for Structured Organic Particulate Systems (C-SOPS). His presentation addressed fundamental engineering principles of continuous manu- facturing and compared its "by-design" equipment and processes to legacy practices. He recommended using virtual designs that account for the characteristic times of existing unit operations and processes. He said to scrutinize—both experimentally and virtually—the process for events that push it outside the steady state and to validate and produce your product within a "control state." Feeding powders will always include some "noise," and in continuous processing that noise can threaten product homogeneity if not properly measured and addressed. He highlighted the opportunity to design process robustness into continuous manufacturing systems, and offered as an example designing back-mixing into a blender to account for the variability of the feeding step. James Litster, professor of chemical engineering and professor of industrial and physical pharmacy at Purdue University, West Lafayette, IN, devoted his talk to con- tinuous granulation in twin-screw granulators. They are used at high throughputs to make detergents, but are also good for developing and scaling low-throughput applica- tions such as pharmaceuticals. Furthermore, they simplify online measurement and control, and allow design opti- mization through regime-separated operation. He discussed twin-screw system variables, which include the powder feed rate, formulation composition, liquid feed rate, granulating liquid composition, method of adding liquid feed, screw speed, shaft length, and screw configuration, which can include conveying, mix- ing, dispersive, and distributive elements. Litster explained how the different elements affected granulation and how to develop a design model. Peter Ojakovo, a formulation scientist at Vertex Pharmaceuticals, discussed how he and his team devel- oped a commercial coating process for its continuous tabletting line using GEA's Omega semi-continuous coater (Figure 2). Unlike traditional pan coaters that rotate slowly and stir a tablet bed, the GEA coater spins quickly (~115 rpm) and the core tablets form a ring around the pan's outside wall. The speed is then reduced to ~92 rpm, and two air knives dislodge the tablets, caus- ing them to cascade through a center-mounted spray. As the coating builds, the rpm can be adjusted, which is han- dled by software linked to a Raman device that tracks the reduction in signal for the API and the increase in signal for the coating material. To polish the coated tablets, the speed is reduced to ~30 rpm. Ojakovo said coating takes less than 20 minutes and typical weight gains are 2.9 to 3.1 percent. RSD variation of coating thickness is 1 percent. The Omega coater han- dles tablets gently, but uses higher-temperature air than conventional pan coaters. Ojakovo said flat tablets were difficult to form into a ring, but the addition of gripper- bars resolved the issue. Robert Meyer, who leads Merck's innovation and technology efforts for small-molecule oral drug products, summarized his team's experimental and operational test- ing of GEA's CDC-50. The tests focused on residence 22 May 2015 Tablets & Capsules Figure 2 How GEA's Omega coater works Wheel filled Ring formation Collapse ring and polish Tablets out Cascade and process Tablet drying Wheel Tablets in Air knives Spray nozzle Exhaust air chute Discharge chute Inlet-air dispersant plate Courtesy of Peter Ojakovo, Vertex